A study of the metabolism of the branched-chain amino acids has revealed a pathway of catabolism of leucine that is catabolic in bacteria and appears to be synthetic in humans. The pathway depends upon the activity of the enzyme, leucine 2,3-aminomutase, which requires adenosylcobalamine as a cofactor. Leucine may be synthesized from iso-fatty acids or from the catabolites of valine. The B-12 dependent enzyme, leucine 2,3-aminomutase, is stimulated by FAD, coenzyme A, NAD, and pyridoxal phosphate. The relationship between enzyme activity and various disease states such as pernicious anemia and maple sugar urine disease will be examined.